Whole-Exome Sequencing Identifies a Novel Variant (c.1538T > C) of TNNI3K in Arrhythmogenic Right Ventricular Cardiomyopathy

BackgroundsArrhythmic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy with a genetic predisposition that can lead to a sudden cardiac death and heart failure. According to the 2010 Task Force Criteria, genetic diagnosis is one of the most important methods, but, so far, only a few genes related to ARVC have been identified. MethodsIn this study, the pathogenic gene of a patient with ARVC was examined using whole-exome sequencing. The plasmids of TNNI3K were constructed, and the effects of the TNNI3K variant was investigated by a real-time polymerase chain reaction (PCR) and western blot. ResultsA novel variant (c.1538T > C) of TNNI3K was identified, with phenotypes of dominant right ventricular (RV) disease preliminarily fulfilling the diagnosis of ARVC. A comprehensive assessment revealed that the variant was pathogenic. We found that this variant would lead to a decrease in the level of TNNI3K mRNA and protein, as well as a decrease in the expression of the RYR2 gene, which further proves that TNNI3K plays an important role in cardiomyopathy and expands the spectrum of the TNNI3K variants. ConclusionIn this study, we reported a TNNI3K variant in ARVC for the first time, and the results not only contribute to the diagnosis of ARVC, but also provide a reference for genetic counseling and promote the understanding of the genetic mechanism of cardiomyopathy.

Automated summary

In this study, a novel variant of TNNI3K was identified in ARVC, which not only contributes to the diagnosis of ARVC, but also provides a reference for genetic counseling, and promotes the understanding of the genetic mechanism of cardiomyopathy.